AMG 319 in HPV Positive and Negative HNSCC

NCT02540928 | Terminated Phase 2

• 1 other identifier: CRUKD/15/004
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to determine whether a drug called AMG 319 has an effect on a patient's own immune response to head and neck cancer squamous cell carcinoma (HNSCC). This study is specifically for patients who are having surgery to treat their HNSCC

Conditions

Human Papillomavirus (HPV); Positive or Negative Head and Neck Squamous Cell Carcinoma (HNSCC) of the Hypopharynx, Oropharynx, Oral Cavity, Supraglottis or Larynx

Outcome Measures

Primary Outcomes (2)

• Changes in CD8+ effector T cell numbers in tumour tissue

  Screening and Surgery

• Treatment emergent adverse events

  Assessed until 60 days after a patients last dose

Secondary Outcomes (2)

• Steady State AMG 319 concentration in blood

  Days 8, 15 pre dose & Day 22

• Changes in tumour size

  Screening and Pre-surgery

Study Arms (2)

AMG 319 Hydrate

EXPERIMENTAL

Up to 36 patients will be randomised into the Active Treatment arm to receive AMG 319 400 mg once daily administered orally for a minimum of 20 days and a maximum of 29 days prior to resection surgery

Drug: AMG 319 hydrate

Placebo

PLACEBO COMPARATOR

Up to 18 patients will be randomised into the Placebo arm to receive Placebo once daily administered orally for a minimum of 20 days and a maximum of 29 days prior to resection surgery

Drug: Placebo

Interventions

AMG 319 hydrate DRUG

AMG 319 Hydrate

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven HNSCC of the hypopharynx, oropharynx, oral cavity, supraglottis or larynx (except T1 glottic tumours) for whom surgery with curative intent ± post operative radiotherapy or chemoradiotherapy is considered the primary treatment of choice. Surgery should be scheduled to take place no sooner than 21 days and no later than 30 days post first dose of AMG 319 or placebo.
• Patients considered fit to undergo curative resection surgery.
• Haematological and biochemical indices within the ranges shown below:
• Laboratory Test Value required
• Haemoglobin (Hb) ≥100 g/L
• Absolute neutrophil count ≥1.5 x 109/L
• Platelet count ≥100 x 109/L
• Bilirubin ≤1.5 x upper limit of normal (ULN) Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤2.5 x ULN
• Alkaline Phosphatase (alk phos/ALP) ≤2.5 x ULN
• Amylase ≤2.0 x ULN
• Calculated creatinine clearance (using the Wright or Cockcroft-Gault formula) ≥50 mL/min
• years or over at the time informed consent is given.
• Written (signed and dated) informed consent and capable of co-operating with treatment and follow up.

You may not qualify if:

• Prior radiotherapy, immunotherapy, chemotherapy or other anti-cancer therapy (excluding surgery) for current HNSCC.
• Patients should be excluded from the trial if they have active or previous malignancies of other types which in the Investigator's opinion would mean they are not a good candidate for the clinical trial.
• Female patients who are able to become pregnant (or already pregnant or lactating). However, those patients who have a negative serum or urine pregnancy test before enrolment and agree to use two highly effective forms of contraception (oral; injected or implanted hormonal contraception and condom; have an intra uterine device and condom; diaphragm with spermicidal gel and condom) effective at the first administration of AMG 319, throughout the trial and for 6 months afterwards are considered eligible.
• Male patients with partners of child bearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception \[condom plus spermicide\] effective at the first administration of AMG 319, throughout the trial and for 6 months afterwards). Men with pregnant or lactating partners must be advised to use barrier method contraception (for example: condom plus spermicidal gel) to prevent exposure to the foetus or neonate.
• Patients unable to swallow oral medications (trial medication must not be chewed, crushed, dissolved or divided).
• Major thoracic or abdominal surgery from which the patient has not yet recovered.
• At high medical risk because of non malignant systemic disease including active uncontrolled infection.
• Active or uncontrolled auto immune disease which may require systemic immunomodulator therapy during the trial treatment period. Exceptions to this are atopic dermatitis and psoriasis not requiring systemic treatment.
• Long term use of systemic corticosteroids with the exception of replacement treatment. Discontinuation of steroid use within seven days prior to receiving the first dose of AMG 319 or placebo would be acceptable. Inhaled and topical steroids are permitted.
• Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV). If there is clinical suspicion of infection this must be ruled out by appropriate serological and PCR testing.
• QTc \>470 msec (Friderica \[QTc F\] correction) or a history or family history of QT prolongation.
• Regular and/or prolonged treatment with medications known to cause QTc interval prolongation within seven days prior to receiving the first dose of AMG 319 or placebo.
• Is a participant or plans to participate in another interventional clinical trial, whilst taking part in this Phase IIa trial of AMG 319. Participation in an observational trial or interventional clinical trial which does not involve administration of an IMP would be acceptable.
• Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical trial.

Sponsors & Collaborators

• Cancer Research UK: lead

Study Sites (5)

Aintree University Hospital - Clatterbridge Cancer Centre

Liverpool, CH63 4JY, United Kingdom

Location

Churchill Hospital, Blenheim H&N Unit

Oxford, OX3 7LE, United Kingdom

Location

Poole Hospital

Poole, BH15 2JB, United Kingdom

Location

Queen Alexandra Hospital, Department of Oral and Maxillofacial Surgery

Portsmouth, PO6 3LY, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Laryngeal Diseases

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Respiratory Tract Diseases; Otorhinolaryngologic Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2015
• First Posted: September 4, 2015
• Study Start: October 1, 2015
• Primary Completion: May 3, 2018
• Study Completion: May 3, 2018
• Last Updated: July 18, 2018

Record last verified: 2018-07

Locations

GB (5)